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Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis

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@article{c011b55b839140e39809a10d5b067791,
title = "Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-na{\"i}ve patients with psychosis",
abstract = "BACKGROUND: Poor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).METHODS: Thirty-nine antipsychotic-na{\"i}ve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.RESULTS: Before treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ.CONCLUSION: Glutamatergic and GABAergic abnormalities in antipsychotic-na{\"i}ve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.",
keywords = "Anterior cingulate cortex, antipsychotic-na{\"i}ve, first-episode psychosis, GABA, glutamate, magnetic resonance spectroscopy, thalamus, treatment outcome",
author = "Bojesen, {Kirsten B} and Ebdrup, {Bj{\o}rn H} and Kasper Jessen and Anne Sigvard and Karen Tangmose and Edden, {Richard A E} and Larsson, {Henrik B W} and Egill Rostrup and Broberg, {Brian V} and Glenth{\o}j, {Birte Y}",
year = "2020",
month = oct,
doi = "10.1017/S0033291719002277",
language = "English",
volume = "50",
pages = "2182--2193",
journal = "Psychological Medicine",
issn = "0033-2917",
publisher = "Cambridge University Press",
number = "13",

}

RIS

TY - JOUR

T1 - Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis

AU - Bojesen, Kirsten B

AU - Ebdrup, Bjørn H

AU - Jessen, Kasper

AU - Sigvard, Anne

AU - Tangmose, Karen

AU - Edden, Richard A E

AU - Larsson, Henrik B W

AU - Rostrup, Egill

AU - Broberg, Brian V

AU - Glenthøj, Birte Y

PY - 2020/10

Y1 - 2020/10

N2 - BACKGROUND: Poor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).METHODS: Thirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.RESULTS: Before treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ.CONCLUSION: Glutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.

AB - BACKGROUND: Poor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).METHODS: Thirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.RESULTS: Before treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ.CONCLUSION: Glutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.

KW - Anterior cingulate cortex

KW - antipsychotic-naïve

KW - first-episode psychosis

KW - GABA

KW - glutamate

KW - magnetic resonance spectroscopy

KW - thalamus

KW - treatment outcome

UR - http://www.scopus.com/inward/record.url?scp=85072276740&partnerID=8YFLogxK

U2 - 10.1017/S0033291719002277

DO - 10.1017/S0033291719002277

M3 - Journal article

C2 - 31524118

VL - 50

SP - 2182

EP - 2193

JO - Psychological Medicine

JF - Psychological Medicine

SN - 0033-2917

IS - 13

ER -

ID: 58198970